PHYSIOLOGY

OF
BLOOD
 Learning Objectives

At the end of this chapter, students should be able to:

List the functions and characteristics of blood
Explain the principal plasma proteins, RBC, WBC and
platelets
Mention types of immunity and the five classes of
immunoglobulin
Describe the phases in hemostasis
Identify the human blood groups
2
 Physical Characteristics and Volume
• Blood is a sticky, opaque fluid with a metallic taste
• It is a viscous fluid connective tissue, which is heavier and
thicker than water.
• Color varies from scarlet (oxygen-rich) to dark red (oxygen-
poor)
• The pH of blood is 7.35–7.45 and its salt content is 0.9%
• Temperature is 38C, slightly higher than “normal” body
temperature
• Blood accounts for approximately 8% of body weight
• Average volume of blood is 5–6 L for males, and 4–5 L for
females

3
 Functions of Blood
• Blood performs a number of functions dealing with:
– Substance distribution
– Regulation of blood levels of particular substances
– Protection

• Blood transports:
– Oxygen from the lungs and nutrients from the digestive tract
– Metabolic wastes from cells to the lungs and to kidneys for
elimination
– Hormones from endocrine glands to target organs

4
 Functions of Blood ….cont’d
• Blood maintains:
– Appropriate body temperature by absorbing and
distributing heat
– Normal pH in body tissues using buffer systems
– Adequate fluid volume in the circulatory system
• Blood prevents blood loss by:
– Activating plasma proteins and platelets
– Initiating clot formation when a vessel is broken
• Blood prevents infection by:
– Synthesizing and utilizing antibodies
– Activating WBCs to defend the body against foreign
invaders

5
 Composition of Blood
• Blood is the body’s only fluid connective tissue

• It is composed of -Liquid plasma (55%) and

-Formed elements (45%)

• Formed elements include:

– Erythrocytes or red blood cells (RBCs)

– Leukocytes or white blood cells (WBCs)

– Thrombocytes or Platelets

• Hematocrit: – the percentage or proportion of blood volume that

is RBCs
6
 Components of Whole Blood

Plasma
(55% of whole blood)

Buffy coat:
leukocyctes and platelets
(<1% of whole blood)

Formed
elements

Erythrocytes
1 Withdraw blood and 2 Centrifuge (45% of whole blood)
place in tube

7
 A. PLASMA
• It is the liquid portion of blood
• It makes up 55% of the blood volume
• Has the osmolality of 300 mosm/l
Composition of plasma
Blood plasma composed of
1. Water (90%)
2. Organic constituents (9%)
– Plasma proteins: albumin, globulins, clotting proteins and
others (7%)
– Lipids, lipoproteins, phospholipids
– Hormones and enzymes
– Nutrients: CHO, vitamins, amino acids, fats
– Metabolic waste products: urea, creatinine
3. Inorganic constituents: electrolytes (1%)
4. Respiratory gases – oxygen and carbon dioxide
8
 Principal plasma proteins
• TPP: 7 g/dl
• There are 3 principal plasma proteins
Albumin: 4 g/dl
Globulin: 2.7 g/dl
Fibrinogen: 0.3 g/dl
• Plasma proteins are synthesized by hepatocytes, lymphocytes,
platelets and endothelial cells
Function of plasma proteins
1. Immunologic function: γ-globulins are immunoglobulins
(antibodies)
2. Nutritional Hemostasis: fibrinogen, prothrombin and most
other clotting factors are plasma proteins
3. Function in starvation
4. Transport of hormones, electrolytes and drugs.
5. pH regulation (buffering function)
6. Maintenance of plasma osmotic pressure
7. Enzymatic and hormonal function
9
 Genesis (Formation) of Blood Cells
• The process by which the formed elements of blood develop is
called hemopoiesis also called hematopoiesis.

• The blood cells begin their lives in the bone marrow from a single
type of cell called the pluripotential hematopoietic stem cells, from
w/c all the cells of the circulating blood are eventually derived.

• The successive divisions of the pluripotential cells form the

different circulating blood cells.

10
 …cont’d
• The intermediate stage cells are very much like the pluripotential
stem cells, even though they have already become committed to a
particular line of cells & are called committed stem cells.
• The different committed stem cells, when grown in culture, will
produce colonies of specific types of blood cells.
• A committed stem cell that produces erythrocytes is called a
colony-forming unit - erythrocyte (CFU-E).
• Likewise, colony-forming units that form the granulocytes &
monocytes have the designation CFU-GM.

11
 Fig. Formation of the multiple different blood cells from original
pluripotent hematopoietic stem cell (PHSC) in the bone marrow.

12
 …cont’d
• About 0.05–0.1% of red bone marrow cells are pluripotent stem
cells.
• In order to form blood cells, pluripotent stem cells in RBM produce
two further types of stem cells
• These stem cells are called myeloid stem cells & lymphoid stem
cells.
• Myeloid stem cells begin their development in red bone marrow &
give rise to RBCs, platelets, monocytes, neutrophils, eosinophils,
& basophils.
• Lymphoid stem cells begin their development in red bone marrow
but complete it in lymphatic tissues.
– They differentiate into cells from w/c the T & B lymphocytes
develop.

13
Hemopoiesis

14
 Hemopoiesis regulating factors

• Hemopoiesis is chemically regulated by several

families of cytokines:
– Colony stimulating factors (CSFs): GM-CSF, G-
CSF, M-CSF
– Interleukines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8,
IL-10, and etc)
– Platelet derived growth factor (PDGF)
– Thrombopoietic stimulating factor (TSF)
– Erythropoietin, GH, T3/T4, androgens
(Testosterone)

15
 ERYTHROCYTES (RED BLOOD CELLS)
Function
• Transport of O2 and CO2
• Regulation of acid-base balance
• Major content of RBCs is Hb (97% )
• Size: Diameter 7.5 µm
Thickness 1 and 2 µm
• Shape: Biconcave disk
No nucleus, no organelles
• RBC Count: M = 5.2 millions/mm3
F = 4.6 millions/mm3
(1 mm3 = 1 µl)
• Hematocrit: The percentage of blood cells
M = 42-48%
F = 38-43%
• Filled with hemoglobin Hb = 1/3 Hct
• Plasma membrane of RBCs is comprised of
flexible proteins
– Allow them to change shape as necessary
– ATP is generated anaerobically
16
17
 Production of Erythrocytes
• Hematopoiesis – blood cell formation

• Hematopoiesis occurs in the red bone marrow

Areas of production of RBCs

• During early IUL: Liver, spleen and lymph nodes
• Late IUL and in infants: All red marrow of all bones
• In children and adults:
 RBM of vertebrae, sternum, ribs, pelvis, skull bone and
the proximal and distal part of long bones.
 The shaft of long bones is filled with YBM.
18
 Production of Erythrocytes: Erythropoiesis

Proliferation phase Maturation phase

Regulation and Requirements for Erythropoiesis

• Circulating erythrocytes: – the number remains constant and

reflects a balance between RBC production and destruction
– Too few RBCs →leads to tissue hypoxia
– Too many RBCs → causes increased blood viscosity
• Erythropoiesis requires diets rich in:

– Proteins, lipids, and carbohydrates

– Iron, vit-B12, folic acid, vit-A and vit-C

– Vit-B12 is essential for RBC maturation

20
 Regulation and Requirements …cont’d

• Erythropoiesis is hormonally controlled. Hormones accelerating

erythropoiesis:
– Erythropoietin (EP) from JG-cells and hepatocytes
– GH, T3/T4, Androgens
– Intrinsic factor from parietal cells of the stomach

• Liver plays a critical role in RBC formation as site of globin

synthesis, as a storage area of iron and vit-B12

21
Fig. Function of the
erythropoietin
mechanism to
increase production
of RBCs when
tissue oxygenation
decreases.

22
 Erythropoietin Mechanism
Imb
ala
nce
Start
Normal blood oxygen levels
Stimulus: Hypoxia due to
Imb
a la
decreased RBC count,
nc e
decreased availability of
Increases O2 in blood, or increased
O2-carrying tissue demands for O2
ability of blood
Reduces O2
levels in blood

Erythropoietin
Enhanced Kidney 85% and
stimulates red
erythropoiesis bone marrow liver 15 % releases
increases RBC erythropoietin
count
23
 Hormonal Control of Erythropoiesis
• Erythropoietin (EPO) release by the kidneys is triggered by:

– Hypoxia due to decreased RBCs or reduced quantity of Hb

– Decreased oxygen availability
– Increased tissue demand for oxygen

• Enhanced erythropoiesis increases the:

– RBC count in circulating blood

– Oxygen carrying ability of the blood

24
 Hemoglobin
• Hb in RBCs is meant for transport of respiratory gases
• Normal concentration; 16 g/dl in M and 14 g/dl in F

Composition and synthesis of Hb

– Composed of a protein globin and heme
– The heme part is made up of α-KG and an aa glycine
– 2 α-KG + glycine results in Pyrrole
– 4 pyrrole form 1 protoprophyrin-III
– 1 protoprophyrin-III combines with Iron to form heme
– 4 heme molecules conjugated with 4 globin molecules to
form Hb

25
 Hemoglobin…cont’d

Types of Hb 1. Adult Hb (HbA-α2 β2)

2. Fetal Hb (HbF -α2 γ2)

3. Sickled Hb (HbS - α2 β2)

• Sickled Hb, in two of the β-chains at position-6 an amino acid

valine is wrongly substituted for glutamate
• In adult Hb, the globin part has 4 polypeptide chains

2 α-chains, each made up of 141 AA residues

2 β-chains, each made up of 146 AA residues

26
 Hemoglobin…cont’d

• The normal Hb becomes 100% saturated when blood is

equilibrated with 100% O2 (PO2, 760 mm Hg).

• 1gm of Hb when fully saturated combines with 1.34 ml of O2.

– Hb concentration is an index of O2 carrying capacity of the

blood.

• Thus, normal values of O2 carrying capacity in males is 1.34 x

16 = about 21 ml of O2, & in females is 1.34 x 14 = about 18.5

ml of O2.

27
Structure of Hemoglobin

28
 Hemoglobin…cont’d
• Hemoglobin reversibly binds with oxygen and most oxygen in
the blood is transported in combination with hemoglobin
• Each heme group bears an atom of iron, which can bind to one
oxygen molecule

• Each hemoglobin molecule can transport four molecules of

oxygen
• Oxyhemoglobin: – hemoglobin bound to oxygen

– Oxygen loading takes place in the lungs

• Deoxyhemoglobin – hemoglobin after oxygen diffuses into

tissues 29
 Hemoglobin…cont’d
• Carbaminohemoglobin – hemoglobin bound to carbon dioxide

– Carbon dioxide loading takes place in the tissues and is

returned to lungs to be eliminated in expired air
• Carboxyhemoglobin or carbon monoxyhemoglobin is a
compound of Hb with CO.
• The affinity of Hb for CO is much more (200-250 times) than
its affinity for O2.

– Because of this the CO displaces O2 from Hb, thereby

reducing the O2 carrying capacity of the blood.

30
 Destruction of Erythrocytes
The life span of an erythrocyte is 100–120 days

Old erythrocytes become rigid and fragile with age, and their
hemoglobin begins to degenerate
Dying erythrocytes are engulfed by macrophages
Heme and globin are separated and the iron is salvaged for reuse
The heme part is converted into bilirubin
Bilirubin is the main component of biliary secretion

31
 RBC Life Cycle…cont’d
The breakdown products of erythrocytes are recycled, as follows:
1.Macrophages in spleen, liver, or RBM phagocytize ruptured & worn-
out RBCs.

2.The globin & heme portions of the Hb are split apart.

3.Globin is broken down into AAs, which can be reused to synthesize

other proteins.

4.Iron is removed from heme portion in the form of Fe3+, which

associates with the plasma protein transferrin, a transporter for Fe3+ in
the bloodstream.

5.In muscle fibers, liver cells, & macrophages of spleen & liver, Fe3+
detaches from transferrin & attaches to an iron-storage protein called
ferritin. 32
 …cont’d
6. Upon release from a storage site or absorption from the GI
tract, Fe3+ reattaches to transferrin.
7. Fe3+–transferrin complex is then carried to red bone marrow,
where RBC precursor cells take it for use in Hb synthesis.
8. Erythropoiesis in red bone marrow results in the production
of RBCs, which enter the circulation.
9. When iron is removed from heme, the non-iron portion of
heme is converted to biliverdin, & then into bilirubin.

33
 RBC Life Cycle, cont’d
10. Bilirubin then enters the blood & is transported to the liver.
11. In liver, bilirubin is released by liver cells into bile, w/c passes into
the small intestine & then into the large intestine.

12. In large intestine, bacteria convert bilirubin into urobilinogen.

13. Some urobilinogen is absorbed back into blood, & converted to a
yellow pigment called urobilin, w/c excreted in urine.
14. Most urobilinogen is eliminated in feces in form of a brown
pigment called stercobilin, which gives the color of feces.

34
Formation and destruction of RBCs, and the recycling of hemoglobin
components. 35
 Destruction of Erythrocytes …
Jaundice
– Yellow coloration of the skin and sclera
– Due to excessive bilirubin in plasma
– Normal plasma bilirubin level is 0.5 mg/dl
– In case of jaundice, bilirubin level is elevated up to 40 mg/dl
– The skin and the sclera look yellow when bilirubin level rises
>1.5 mg/dl
Causes/types of jaundice
1. Hemolytic jaundice: ↑RBC destruction
2. Obstructive jaundice:
a. Obstruction of bile ducts
b. Damage to the liver cells

36
 Iron metabolism
• Iron is essential for the formation of Hb, Mb and a cofactor for
cytochrome enzymes, peroxidases and catalases.
• A normal adult contains a total of 4 g of iron, needs 1 mg/day
• Iron exists in the body in different forms
65% in the form of Hb

4% in the form of Mb

1% in the form of cytochromes
0.1% in combination with transferin

15-30% stored in the liver in the form of ferretin and

hemosidrin
37
 Iron metabolism….cont’d

Absorption of Iron
• Ferrous form (Fe2+) is better absorbed than ferric form (Fe3+)
• Ascorbic acid facilitates absorption of ferrous
• Liver produces apoferretin which is capable of combining
reversibly with iron.
• Fe + ferretin absorbed by pinocytosis in the duodenum & jejunum.

• After being metabolized, will be eliminated with feces & urine.

38
 Erythrocyte Disorders
• It is a condition char/zed by:
– A decrease in the hemoglobin level

– ↓ in RBC count or both leading to decrease in the O2

carrying capacity of the blood.
• Signs/symptoms include
– Fatigue
– Paleness
– Shortness of breath and
– Chills
39
 ANEMIA
• Anemia means deficiency of Hb in the blood, which can be
caused by either too few RBCs or too little Hb in the cells.
Types of Anemia
1. Deficiency anemia: caused by deficiency of vit-B12, folic
acid, Iron, proteins and trace elements
2. Aplastic anemia: depression of BM due to irradiation, drugs
and leukumia
3. Hemolytic anemia: prematurely ruptured erythrocytes or
formation of fragile RBCs due to sickle cell, thalassimia,
transfusion reaction, snake venoms, malaria, erythroblastosis
fetalis
4. Bleeding (blood loose anemia or hemorrhagic anemia): result
of acute or chronic loss of blood

40
 …cont’d
Iron deficiency anemia
• Common in infants and females
• Results from:
– Inadequate intake of iron-containing foods
– Impaired iron absorption
– Treated with a replacement therapy
Pernicious anemia
Causes:
 Deficiency of Intrinsic Factor secondary to gastroctomy,
gastric atrophy, defective IF secretion
Treatment:
 IV injection of vit-B12 through the whole life

41
 Sickle Cell Anemia
• Sickle-cell anemia: results from a Normal RBC
defective gene
– Single amino acid substitution in the
beta chain
– This defect causes RBCs to become
sickle-shaped after oxygen is released
to tissue
– RBC becomes rigid and can get stuck
in blood vessels
• Tissue hypoxia: severe pain and
organ damage
– More rapid destruction of RBC’s
• Fatigue
• Advantage of having sickle shaped Sickle RBC
RBCss??? 42
Prevalence of Sickle Cell Anemia in Different Ethnic Groups
 Polycythemia
Polycythemia: ↑RBCs count > 6 million/mm3
Causes
1. Chronic hypoxia: -High altitude
-Heart failure
-Respiratory failure
2. Primary over-activity of the bone marrow
Effect: ↑increase blood viscosity, ↓VR, ↑BF, & ↑BP
Types of Polycthemia
─ Physiologic polycythemia. A common type of 2ry
polycythemia, occurs in natives who live at high altitudes,
where the atmospheric O2 is very low.
─ Primary polycythemia/Polycythemia vera (Erythremia)
It is a pathological condition in which the RBCs count may
reach 7–8 million/mm3 & Hct level of 60–70%. 44
 LEUKOCYTES (WBCS)
• It is the only blood components that contain nucleus, and other
organelles
• Make up 1% of the total blood volume
• Less numerous than RBCs
– Normal WBC count: 5,000 – 11,000/mm3 =
Average:7000/mm3
• Leukopenia: ↓in WBC count
• Leukocytosis-↑in WBC count
• Function: defense/protection against disease
45
 Types of WBCs
Granular leukocytes Agranular leukocytes
PMN-cells: Neutrophils Monocytes
Eosinophils Lymphocytes
Basophils

WBC differential count

Neutrophils: 50-60% (60%), 3000-7000/mm3
Eosinophils: 1-4% (2.4%), 100-440/mm3
Basophils: 0.3-0.5% (0.4%), 20-50/mm3
Monocytes: 2-8% (5.3%), 100-700/mm3
Lymphocytes: 20-40% (30%), 1500-3500/mm3

46
 Types of White Blood Cell

Macrophages

47
Formation of leukocytes

48
 Primary Functions of WBCs
1. Neutrophils
• The most abundant WBCs
• Have multi-lobed nuclei (PMN)
• The first line of defense
• Phagocytic cells (ingest bacteria)
• Properties:
Diapedesis means of extravasation
The passage of blood cells through the unruptured
wall of a blood vessel into the surrounding tissues
Chemotaxis: attracted to certain chemicals
Opsonization: the rendering of bacteria and other cells
subject to phagocytosis
Release of histamine
49
 Primary Functions of WBCs ...
2. Eosinophils
– Eosinophils account for 1–4% of WBCs
– Absorb histamine during allergic conditions so that lessen the
severity of allergies
– Increase in number during parasitic infection (eosinophilia)
– Produce hydrolytic enzymes to kill big parasites

3. Basophils
– Account for 0.5% of WBCs
– They resemble mast cells
– Synthesize & store histamine, bradykinin, serotonin and
heparin

50
 Primary Functions of WBCs ...
4. Monocytes
– Monocytes account for 4–8% of WBCs
– They are highly phagocytic cells
– They are the largest WBCs
– They leave the circulation, enter tissue, and differentiate
into macrophages

51
 The tissue macrophage system (reticulo-endothelial system)
Monocytes are formed in the bone marrow

Enter the circulation

Leave the circulation & enter the tissue,

↑size, ↑lysosomal activities

Become tissue macrophages

Lungs Skin Liver Brain Bone Spleen,

Alveolar Histocytic Kupffer Microglial Osteoclasts lymph nodes
Macrophages cells cells cells Reticular cells

52
 Leukocytes Disorders: Leukemia
• Leukemia refers to cancerous conditions involving white blood
cells (causing proliferation of immature WBCs)
• Leukemias are named according to the abnormal white blood cells
involved
– Myelocytic leukemia: – involves myeloblasts
– Lymphocytic leukemia: – involves lymphocytes
• Acute leukemia
– Rapid onset (children and adults)
• Chronic leukemia
– Symptoms develop slowly
(mostly in adults)

53
 Leukemia…cont’d
Immature white blood cells are found in the bloodstream in
all leukemia in large number.
Bone marrow becomes totally occupied with cancerous
white blood cells
The WBCs produced in numerous, but are not functional
Death is caused due to internal hemorrhage and massive
infections

54
 Symptoms of Leukemia
• Night sweats and fever
• Infections
• Weakness/chronic fatigue
• Headaches
• Bleeding/bruising
• Joint/bone pain
• Abdominal swelling from
enlarged spleen
• Lymph node swelling
• Weight loss
Treatments: include
irradiation, anti-leukemic drugs,
and bone marrow transplants

55
 Immunity
• Immunity is body's ability to resist or eliminate potentially
harmful foreign materials or abnormal cells
• Consists of the following activities:
– Defence against invading pathogens (viruses & bacteria)
– Removal of 'worn-out' cells (e.g., old RBCs) & tissue debris
(e.g., from injury or disease)
– Identification & destruction of abnormal or mutant cells
(primary defence against cancer)
– Rejection of 'foreign' cells (e.g., organ transplant)

56
 Types of Immunity
Two types:
A. Non-specific immunity or Natural/innate immunity
Examples:
 Phagocytosis
 HCl in the stomach
 Skin barrier
 Lysozymes in saliva
 Interferons:
 proteins made and released by host cells in
response to the presence of pathogens such as
viruses, bacteria, parasites or tumor cells.

57
 Types of Immunity...cont’d
B. Specific immunity or acquired/adaptive immunity
Features:
 Specific
 Memory:
 The ability to remember and respond more robustly
against a second encounter with the same pathogen
 Recognition of self and non-self:
 The ability to distinguish between the body’s own
cells, recognized as “self,” and foreign cells, or
“non-self
 Involves lymphocytes (a type of WBC) called T
lymphocytes (T cells) & B lymphocytes (B cells).

58
 Types of acquired immunity

1. Humoral immunity/Antibody mediated immunity

– B-Lymphocytes are specialized for this type of immunity
2. Cellular immunity/Cell mediated immunity
– T-Lymphocytes are specialized for this type

59
 Lymphocytes
• They are the major soldiers in immune system battles.
• Most lymphocytes continually move among lymphoid tissues,
lymph, & blood, spending only a few hours at a time in blood.
 Thus, only a small proportion of the total lymphocytes are
present in the blood at any given time.
• Three main types of lymphocytes are B cells, T cells, &
natural killer (NK) cells.
• B cells are particularly effective in destroying bacteria &
inactivating their toxins.

60
 Lymphocytes …cont’d

• T cells attack viruses, fungi, transplanted cells, cancer cells, &

some bacteria, and are responsible for transfusion reactions,
allergies, & the rejection of transplanted organs.
 Immune responses carried out by both B cells & T cells
help combat infection & provide protection against some
diseases.
• Natural killer cells attack a wide variety of infectious microbes
& certain spontaneously arising tumor cells.

61
 Lymphocytes and their origin
Bone Marrow (IUL)
Lymphoblasts (lymphocyte stem cells)

Lymphocytes

Thymus gland Bursa Fabricus in Birds

Bone marrow in man

T-Lymphocytes B-Lymphocytes

Enter the circulation

Filtered in to lymphoid tissues
(Lymph node, Spleen),

62
 Activation of B-Lymphocytes for humoral immunity

+ B-Lymphocytes
in lymphoid tissues

Antigens Activated B- cells

Macrophages
(Antigen presenting cells) Actively divided

Intermediate
Cells: clones

Memory B-cells Plasma B-cells

Dormant in the 1o-exposure Produce antibodies
Vigorous during 2nd-exposure γ-Immunoglobulins 63
 Activation of B-cells to make antibodies
• The B cell uses its receptor to bind
a matching antigen, which it
proceeds to engulf and process.
• Then it combines a fragment of
antigen with its special marker, the
class II protein.
• This combination of antigen and
marker is recognized and bound by
a T helper cell carrying a matching
receptor.
MHC=Major histocompatibility complex 64
 Activation of B-cells to ...cont’d
• The binding activates the T cell,
which then releases interleukins
– That transform the B cell into
an antibody- secreting plasma
cell.

65
 Immunoglobulins
• B-cells that bind with an antigen will
subsequently differentiate into Plasma
cells & Memory cells
 Plasma cells - begin to produce
antibodies (up to 2,000 per second)
 Memory cells - remain dormant until
a person is again exposed to the same
antigen
• There are 5-classes of antibodies (γ-
Immunoglobulins, Ig)
 IgA, IgE, IgD, IgG and IgM
66
 Five classes of Immunoglobulin
• IgM - B cell surface receptor for antigen
attachment, usually combines in star-shaped
clusters.
 secreted early in an immune response, it
tends to remain in the blood stream,
where it is very effective in killing
bacteria.
• IgG - most abundant antibody; produced in
large numbers
• IgE - mediator for common allergic
responses (hay fever (allergic rhinitis),
asthma, & hives)

67
 Five classes of Immunoglobulin…cont’d

• IgA - found in secretions of digestive,

respiratory, urinary, & reproductive systems,
as well as in breast milk and in tears
• IgD - found on the surface of many B cells;
function is unknown

68
 Active immunity Vs. Passive immunity

• Active ('natural') = production of antibodies as a result of

exposure to an antigen (vaccine)
• Passive = direct transfer of antibodies formed by another
person (or animal), e.g., transfer of IgG antibodies from
mother to fetus across placenta or in colostrum ('first milk')
OR treatment for rabies or poisonous snake venom

69
 Mechanism of action of antibodies
• Antibodies act mainly in two ways to protect the body against
invading agents:
1. By direct attack of invaders
− Agglutination of microbial agents
− Precipitation of antigens
− Neutralization of toxic antigens
− Lyses or killing of infectious agents
2. By activation of the complement system

70
 Complement System 
• The complement system consists of a series of proteins that
work to "complement" the work of antibodies in destroying
bacteria. 
• Complement proteins circulate in the blood in an inactive form.
• The so-called "complement cascade" is set off when the first
complement molecule, C1, encounters antibody bound to
antigen in an antigen-antibody complex.
• Each of the complement proteins performs its specialized job in
turn, acting on the molecule next in line.
• The end product is a cylinder that punctures the cell membrane
and, by allowing fluids molecules to flow in and out, dooms the
target cell.

71
…cont’d

72
 Activation of T-Lymphocytes for cellular immunity

+ T-Lymphocytes
in lymphoid tissues

Activated T- cells
Antigens Actively divided and
Macrophages
differentiated
(Antigen presenting
cells)
Intermediate
Cells: clones

Memory T-cells
Helper T-cells Suppressor
Killer (Cytotoxic) T-cells •Stimulate B-cells Dormant in the
•Produce cytotoxic 10-exposure T-cells
•Stimulate killer cells
Chemicals to kill Ag •Stimulate macrophages Vigorous during
•Stimulate macrophages •Produce lymphokines 2nd-exposure 73
 Immunodeficiency disease
Causes of immunodeficiency

– Exposure to high frequency radiation

– HIV/AIDS

– Certain drugs e.g. Cortisone

74
 PLATELETS

• Structures:
 Shape- discoid
 Diameter- 1-4um
 Don’t have nuclei
 Have contractile proteins (actin, myosin & thrombosthenin)
 Contain mitochondria, endoplasmic reticulum and golgi
apparatus
• Synthesize- prostaglandins, fibrin stabilizing factor, growth
factors, serotonin and other chemicals.

75
 PLATELETS…cont’d

• Have special glycoprotein coating.

• Removal- by macrophages.
• Platelets function in the clotting mechanism by forming a
temporary plug that helps seal breaks in blood vessels
• Normal platelet count is 150,000 – 300,000/mm3 (Av=
250,000/mm3)

76
 Genesis of Platelets (thrombocytopoisis)
• The stem cell for platelets is the hemocytoblast
• The sequential developmental pathway is: hemocytoblast →
megakaryoblast→ promegakaryocyte, → megakaryocyte →
platelets

77
 PLATELETS…cont’d

Inactive platelets Active platelets

78
 PLATELETS…cont’d

• Thrombocytopenia: low number of platelets

• Thrombasthenia: a decrease in function of
platelets
• Thrombocytosis: an increase in the number of
platelets

79
 Hemostasis
• A series of reactions designed for stoppage of bleeding
• During hemostasis, three phases occur in rapid sequence
1. Vascular spasm: immediate vasoconstriction in
Oncology:
response to injury B Cell Lymphoma
2. Platelet plug formation
3. Coagulation (blood clotting)

80
 1. Vascular spasm
• Local vasoconstriction of a ruptured blood vessel that is caused
by:
 Reflex sympathetic discharge and
 Local myogenic contraction of the vascular wall

• In effect both reaction minimize rate of bleeding by narrowing

the diameter of the hole (rupture) on the wall of the blood
vessels
• Importance:- blood flow is reduced.

N.B- for smaller vessels, constriction is the result of thromboxane

A2 released from platelets.

81
 2. Platelet Plug Formation
• Platelets help to stop blood loss from damaged blood
vessels by forming a platelet plug.
• Platelet plug is very effective in preventing blood loss in a
small vessel.
• A platelet plug can stop blood loss completely if the hole
in a blood vessel is not too large.
• Their granules also contain chemicals (clotting factors,
ADP, ATP, Ca2+ & serotonin) that, once released, promote
blood clotting.
• Also contain enzymes that produce thromboxane A2, a
prostaglandin; fibrin-stabilizing factor, w/c helps to
strengthen a blood clot.
82
 …cont’d
• Normally, platelets do not stick to each other or to the endothelial
lining of blood vessels
• Platelets have a short life span, normally just 5 to 9 days.
• Aged & dead platelets are removed by fixed macrophages in the
spleen & liver.
• Upon damage to blood vessel endothelium (which exposes
collagen) platelets:
– Adhere to collagen
– Stick to exposed collagen fibers and form a platelet plug
– Release serotonin and ADP, which attract additional platelets
• The platelet plug is limited to the immediate area of injury

83
 3. Coagulation
• A set of reactions in which
blood is transformed from a
liquid to a gel (clot).
• It is slow but has long lasting
effect to stop bleeding
• Coagulation is formed
primarily of fibrin threads (or
polymers), but also including
blood cells & platelets.
• Coagulation follows intrinsic
and extrinsic pathways

84
 Blood clotting factors
1. Factor-I: Fibrinogen
2. Factor-II: Prothrombin. α1- globulin
3. Factor-III: Tissue factor, tissue thromboplastin, a
phospholipoprotein
4. Factor-IV: Calcium ion, essential for clotting
5. Factor-V: Labile factor, β-globulin. Defiency leads
to parahemophelia
6. Factor-VII: Stable factor, α1-glubulin
7. Factor -VIII: Antihemophilic factor-A, β2-globulin
8. Factor -IX:Christmas factor, AHF-B, α1- globulin
9. Factor -X: Stauter-power factor
10. Factor-XI: AHF-C, plasma thromboplastin anticident
γ-globulin
11. Factor-XII: Contact factor, Hagen factor, glass factor
12. Factor-XIII: Fibrin stabilizing factor, β-globulin,
polymerizes fibrin threads 85
 Additional clotting factors
• Prekallikrin: Fletcher factor, β-globulin
• Kininogen: α-globulin
• Van Willebrand factor: For platelet adhesion

Vitamin-K and blood clotting

• Vitamin-K is required for the synthesis of clotting factors: II,
VII, IX and X
• Vitamin-K deficiency occurs in case of obstructive jaundice,
chronic diarrhea, liver disease (hepatitis, cirrhosis, malignancy)
• Blood clotting factors are produced by
Liver
Platelets
Endothelial cells
86
 Stages of Blood Coagulation
• Coagulation undergoes three steps of reactions:

1. Formation of prothrombin activators through

• The intrinsic pathway
• The extrinsic pathways

2. Conversion of prothrombin into thrombin by the action of

prothrombin activators (prothrombinase)
3. Conversion of fibrinogen into fibrin thread by the action of
thrombin

87
Formation of prothrombin activators

F-III

88
Coagulation

89
 Clot Retraction and Repair
• Clot retraction: stabilization of the
clot by squeezing serum from the
fibrin strands
• Repair:
– Platelet-derived growth factor
(PDGF) stimulates rebuilding of
blood vessel wall
– Fibroblasts form a tissue patch
– Stimulated by vascular
endothelial growth factor
(VEGF), endothelial cells
multiply and restore the
endothelial lining

90
 Fibrinolysis: Dissolution of clot
Steps:
Thrombin
+Thrombomodulin
Protein-C Activated Protein-C

F-VIIIa VIII Va V

Activates tPA
Plasminogen Plasmin (fibrolysin)

Degradation of Fibrin
91
 Prevention of unwanted intravascular clotting

1. Smoothness of the endothelium: prevents platelet adhesion

2. The presence of intravascular anticoagulants produced by
endothelial cells, platelets and WBCs.
 These anti-caogulants include:
o Thrombomodulin:
– inactivates thrombin
– Initiates the formation of protein-C

– Protein-C inactivates F-V and F-VIII

92
 Prevention of unwanted …cont’d

o Formation of tissue plasminogen activator (tPA), which

catalyzes the conversion of plasminogen into plasmin
(fibrinolysin).

o Formation of prostaglin (PGI2)

o Formation of anti-thrombin-III, which blocks the action of F-

F-XII, F-XI, F-X and F-II (thrombin)
o Heparin produced by mast cells and basophils: It is combined
with AT-III to block the action of thrombin

93
 Anticoagulants
Anticoagulants are used to prevent unwanted blood clotting
1. In vitro anticoagulants
 Ca-trapping chemicals: Citrate, EDTA, Oxalate,
Heparin, Defibrination (removal of Fg)
2. In vivo anticoagulants:
 Heparin
 Anti-thrombin-III
 Protein-C
 Prostaglandin-I2
 Oral anticoagulant drugs
– Dicumarol and warfarin: Vit-K inhibitors

94
 Prevention of Undesirable Clots

• Substances used to prevent undesirable clots include:

– Aspirin (an anti-prostaglandin): inhibits initiation of
clotting mechanism so platelets are less likely to stick
together
– Heparin: an anticoagulant used clinically for pre- and
postoperative cardiac care
– Warfarin (coumadin): used for those prone to atrial
fibrillation

95
 Hemostasis Disorders
• Thrombus: a clot that develops and persists in blood vessel
– Thrombi can block circulation, resulting in tissue death
and organ failure
– Coronary thrombosis: – thrombus in blood vessel of the
heart
• Myocardial infarction (heart attack)
• Embolus: a thrombus (blood clot) freely floating in the
blood
– Pulmonary emboli: can impair the ability of the body to
obtain oxygen
• 600,000 per year in US causing 60,000 deaths
– Cerebral emboli: can cause strokes
96
 Abnormal intravascular clotting
Thrombo-embolism
Causes:

– Damage to the endothelium e.g. Atherosclerosis

– Sluggishness of blood flow

– Increase in viscosity of blood due to high platelet count or

high RBC count

97
 Embolism
Pulmonary embolism
– 1st or 2nd most common cause of unexplained death
– Usually originates as from deep vein thrombosis that travels
into pulmonary artery and blocks artery
– Risks:
• Post surgical patients
• Prolonged bed rest

• After MI
• After heart bypass surgery
98
 Bleeding Disorders
• Inability to synthesize procoagulants (factors regulating
clotting mechanism) by the liver results in severe bleeding
disorders
– Causes can range from vitamin K deficiency to hepatitis
and cirrhosis
• Inability to absorb fat can lead to vitamin K deficiencies as
it is a fat-soluble substance and is absorbed along with fat
• Liver disease can also prevent the liver from producing bile,
which is required for fat and vitamin K absorption
99
 Bleeding Disorders…cont’d
Haemophilia
• Hereditary sex-linked recessive bleeding disorder in males
XXh x XY
XX, XY hXX, hXY
• Bleeding time is prolonged
There are three types of hemophilia
1. Hemophilia-A: most common type (83% of all cases)
due to lack of F-VIII
2. Hemophilia-B: due to lack of F-IX
3. Hemophilia-C: due to lack of F-XI
Treatment: Replacement thrapy
• Parahemophilia: a state of hemorrhage due to lack of F-V
• Hypoprothrombinemia: liver disease, lack of vit-K
• Afibrinogenemia: liver disease 100
 Bleeding Disorders…cont’d
• Purpura: char/zed by spontaneous hemorrhage in skin.

• Two types: Thrombocytopenic purpura

Thrombosthenic purpura
– Patients have small purple blotches on the skin due to
spontaneous, widespread hemorrhage
– Caused by suppression or destruction of bone marrow
(e.g., malignancy, radiation)
– Treated with whole blood transfusions
101
 HUMAN BLOOD GROUPS
• Grouping depends on the presence of antigens
(agglutinogens) on the surface of RBCs
• RBCs contain protein/glycoproteins/lipoproteins on
their surface with antigenic effect
• These antigens are:
– Unique to the individual
– Recognized as foreign if transfused into another
individual who does not have those same antigens
on RBC membrane
• Presence or absence of these antigens is used to
classify blood groups
102
 Major blood groups

• Over 14 blood groups and over 100 antigens are

identified from erythrocyts
• Major blood groups are
ABO blood group
Rh system
Other blood groups (medically less important)
MNS system
P, Kell, Kide, Duffy system
Diego, Lutheran system

103
 ABO Blood Group
• Based on the ± of two agglutinogen (A and B), the ABO blood
group can be classified into four types of blood
1. When agglutinogen A is present on RBCs, the blood is type-A
2. When agglutinogen B is present on RBCs, the blood is type-B
3. When both agglutinogen A & B exist together type-AB
4. When neither agglutinogen A nor B are present type-O
Genetic combinations that determine blood type
5. OO produces type-O blood
6. AO and AA produce type-A blood
7. BO and BB produce type-B blood
8. AB produces type-AB blood
104
 Agglutinins (antibodies)
In the ABO blood grouping, plasma contains two
genetically determined agglutinins (antibodies):
 Anti-A antibodies (agglutinin-α)
 Anti-B antibodies (agglutinin-β)
Existence of agglutinogen and agglutinins
1. When agglutinogen A is present on RBCs, anti-B ab
2. When agglutinogen B is present on RBCs, anti-A ab
3. When agglutinogen A & B exist together, neither
anti-A nor anti-B abs present in the serum
4. When no agglutinogen on RBCs both anti-A and
anti-B abs are present in the serum
105
Ag-Ab coexistence in the ABO Blood groups

Blood type Antigen Antibody

A A anti-B
B B anti-A
AB A&B Neither
O Neither both anti-A & anti-B

Because the antibodies are large IgM-type

antibodies that do not cross the placenta, ABO
incompatibility between a mother and her fetus rarely
causes problems.
106
 ABO Blood Typing
To determine a blood type, a drop of blood sample
is mixed with a known prepared antibodies
Known agglutinins
Blood
samples Anti-A
Anti-B Blood type
antibody
antibody

1 + ‒ A
2 ‒ + B
3 + + AB
(+) = Agglutination reaction
4 ‒ ‒
(‒) = No agglutination reaction
O
107
 ABO blood group Cross matching
 Cross matching is a means to determine the compatibility of
the blood of donors with that of recipients for blood transfusion.

Recipients blood types

Donors
Blood
types A B AB O

A ‒ + ‒ +
B + _ ‒ +
AB + + ‒ +
O ‒(+) = Agglutination
‒ reaction ‒ ‒
(‒) = No agglutination reaction 108
 Rh Factor
 It was first worked out on Rhesus monkey to the name
Rh-system
 Grouped as Rh+ and Rh- based on the presence or
absence of agglutinogen D on the surface of RBCs
 The presence of agglutinogen on RBCs: Rh+
 Missing agglutinogen on RBCs: Rh-
 Agglutinin (anti-D antibodies) are not normally present
in the serum, produced secondary to exposure of an Rh-
blood to Rh+ blood (antigen-D)

109
 …cont’d
Normally, blood plasma does not contain anti-Rh antibodies.
If an Rh- person receives an Rh+ blood transfusion, however,
the immune system starts to make anti-Rh antibodies that will
remain in the blood.
If a second transfusion of Rh+ blood is given later, the
previously formed anti-Rh antibodies will cause
agglutination & hemolysis of the RBCs in the donated
blood, and a severe reaction may occur.

110
 Erythroblastosis Fetalis (HDNB)
 The most common problem with Rh incompatibility,
hemolytic disease of the newborn (HDNB), may arise
during pregnancy.
 Occurs when an Rh- mother marries an Rh+ father and
conceives an Rh+ fetus
 During delivery, there could be a leakage of Rh+ blood from
the fetus to the circulation of the mother.
 Rh+ blood induces production of anti-D antibodies in the
circulation of the mother. 111
 Erythroblastosis Fetalis…cont’d
 During 2nd conception of Rh+ fetus, anti-D antibodies cross
the placenta and attack RBCs of the fetus
 Treatment
Rho Gam injection after 1st birth which blocks mother
from forming anti-Rh antibody
All Rh- women should receive RhoGAM soon after
every delivery, miscarriage, or abortion.
Limits risk for subsequent births
112
 Blood Transfusions
A transfusion is the transfer of whole blood or blood
components (RBCs only or blood plasma only) into the
bloodstream or directly into the red bone marrow.
A transfusion is most often given to alleviate anemia, to 
BV (e.g., after a severe hemorrhage), or to improve
immunity.
Whole blood transfusions are used:
– When blood loss is substantial
– In treating thrombocytopenia

• Packed red cells (cells with plasma removed) are used to

treat anemia
113
 Blood Transfusions, …cont’d
Precaution during blood transfusion

1. Determine blood group of the patient

2. Determine Rh factor
3. Do cross matching to see compatibility
4. Screen the blood for pathogens
5. Start with slow rate
6. Closely follow the patient

114
 Transfusion Reactions
• Transfusion reactions occur when mismatched blood is
infused
• In an incompatible blood transfusion, antibodies in recipient’s
plasma bind to antigens on the donated RBCs, which causes
agglutination or clumping of the RBCs
• Agglutination is an antigen–antibody response in which
RBCs become cross-linked to one another.
• As a result of the reaction:
o Diminished oxygen-carrying capacity
o Clumped cells impede blood flow
o Ruptured RBCs release free Hgb into the bloodstream
− Circulating Hgb precipitates in the kidneys & causes
renal failure
115
 Diagnostic Blood Tests
• Laboratory examination of blood can assess an
individual’s state of health
• Microscopic examination:
– Variations in size and shape of RBCs: – predictions
of anemia's
– Type and number of WBCs: – diagnostic of various
diseases
• Chemical analysis can provide a comprehensive picture
of one’s general health status in relation to normal
values

116